Vol 21, No 5 (2023)

Relevance. The review is devoted to the analysis of modern ideas about the functional role of connexins in intercellular interactions, their participation in maintaining cellular and tissue homeostasis and in the pathogenesis of diseases of the respiratory system. The possibility of considering connexins as potential targets for targeted therapy is discussed.

The purpose of the study was to consider possible molecular mechanisms of intercellular interactions through gap channels formed by connexins and ways to regulate their work.

Material and methods: analysis and systematization of scientific literature over the past 15 years was carried out in the PubMed, Scopus and Google Scholar databases.

Results. Particular attention in the review is paid to the participation of connexins in gap junctions and hemichannels in the processes of transport of calcium ions, metabolite molecules, ATP and mitochondria across the cell membrane. Disturbances in the regulation of these processes of intercellular interactions make a significant contribution to the pathogenesis of many diseases, in particular diseases of the respiratory system. Deepening the understanding of the molecular mechanisms of the work of various connexins in gap channels will provide an opportunity for the promising development of therapeutic approaches using blocking or stimulating the activity of a specific connexin, taking into account its critical functions in the implementation of intercellular interactions in general.

Introduction. The use of mesenchymal stem cells (MSCs) is recognized as a promising direction for the treatment of diseases with a predominance of inflammation and sclerosis in the pathogenesis, which includes nephrotuberculosis (NT).

Target. Studying the effectiveness of using MSCs in the complex treatment of experimental renal tuberculosis caused by a multidrug-resistant pathogen strain, and assessing the effect of cell therapy on the nature of reparative processes.

Material and methods. NT with MDR was modeled in rabbits by inoculating the renal parenchyma cortex with a suspension of the clinical strain 5582 of Mycobacterium tuberculosis genotype Beijing (10⁶ mycobacteria/0.2 ml). There were 3 groups: 1^st (n=6) – infection control (infected, untreated); 2^nd (n=7) – anti-tuberculosis therapy – ethambutol, bedaquiline, perchlozone, linezolid; 3^rd main group (n=7) – rabbits 2 months after the start of chemotherapy were injected with a single suspension of 5×10⁷ MSCs/2 ml PBS into the lateral vein of the ear. NT was confirmed by the results of Diaskintest^® and computed tomography (CT), and the presence of viable MSCs by confocal microscopy with RKN-26 dye. A histological and morphometric study of the kidneys was carried out. We used the Statistica 7.0 package

Results. The development of NT was confirmed by positive results of Diaskintest^® and CT data (18 and 30 days after infection, respectively). 3 months after infection, only in group 1, foci of specific inflammation remained in the kidney tissue and pronounced glomerular changes were noted. In rabbits of the 3^rd group, compared to the 2^nd group, a low width of the medulla was revealed, as well as parameters of the area of interstitial fibrosis and collagen area, and higher values of glomerular cellularity.

Conclusion. The participation of MSCs in complex therapy of NT led to a complete regression of specific inflammation in the kidney tissues, acceleration of reparative processes, and contributed to the preservation of the filtration capacity of the kidneys and the efficiency of urine excretion.

Introduction. Tuberculosis is a socially significant disease, which is based on chronic granulomatous inflammation with the formation of fibrosis. The signaling molecules CD44 and ICAM-1 play an important role in the process of migration of immune cells from the bloodstream to the site of inflammation. CD44 is an integral cellular glycoprotein that plays an important role in cell-cell interactions, cell adhesion and migration. The strength of this interaction is ensured by the interaction of ICAM-1 with the LFA-1 antigen located on the surface of leukocytes. Thus, studying the expression levels of CD44 and ICAM-1 during the development of the tuberculosis process will expand our understanding of the involvement of immune cells in the pathomorphism of the disease.

The purpose of the study was to study the expression of markers of migration and adhesion of lymphocytes CD44 and ICAM-1 at various degrees of inflammatory activity in pulmonary tuberculoma.

Methods. The object of the study was tuberculoma, as a clinical form of pulmonary tuberculosis. Using immunohistochemistry and morphometry, the relative expression area of the CD44 and ICAM-1 proteins was determined depending on the degree of activity of the tuberculosis process.

Results. The level of relative expression of ICAM-1 in granulomas did not differ significantly from the degree of activity of the tuberculosis process. A decrease in the level of CD44 expression was observed with the 4^th degree of activity of the tuberculosis process (widespread active inflammatory changes with beginning progression).

Conclusion. The expression level of ICAM-1 remained constant at all stages of tuberculoma pathomorphosis, while the CD44 expression level was significantly associated with the pathomorphosis of the disease, reaching minimum values at the 4^th degree of activity of the pathological process. The data obtained indicate the constant involvement of ICAM-1 in the mechanisms of cell adhesion at all stages of granuloma formation. Low levels of CD44 expression in tuberculomas with grade 4 inflammatory changes reflect the cessation of migration of committed immune cells to the site of inflammation, thereby providing conditions for either stabilization of the pathological process by fibrosis of the granuloma, or, conversely, for the progression of the inflammatory process.

Introduction. Recently, a new approach to visual response has been discussed, based on the use of optical signals of a heavy structure, manifested by fractal dynamics. However, the molecular mechanisms of action of fractal phototherapy (FF) have not been studied.

Purpose of the study: to study the effect of low-intensity fractal optical stimulation on the intraocular production of neurotrophic cytokines in an in vivo experiment.

Material and methods. The material for the study was the vitreous body (VH), isolated from the enucleated eyes of 17 healthy Soviet Chinchilla rabbits. 14 animals, depending on the duration of FF courses, were divided into five groups. 3 rabbits (6 eyes) made up the control group. In this work we used an original device for conducting FF in laboratory animals with two emitters. Photostimulation sessions were carried out daily. The duration of each FF session was 20 minutes. The duration of FF courses for different rabbits ranged from 7 to 180 days. Using enzyme immunoassay, the concentrations of 5 mediators were determined in vitreous samples: brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), interleukin (IL)-6, IL-1β and pigment epithelium dependent factor (PEDF). The results were recorded using a Cytation 5 multifunctional photometer.

Results. BDNF and PEDF were detected in 100% of ST test samples of the main and control groups of animals. IL-1β and CNTF were absent in all biomaterial samples. In only one case, IL-6 was detected in a small concentration in the material from an experimental eye at late stages of FF. This work was the first to study the dynamics of intraocular production of neurotrophic factors under the influence of fractal photostimulation. Individual analysis demonstrated multidirectional changes in PEDF concentration (relative to normal levels) in the early stages of FF, namely: An increase in the intraocular content of this cytokine was observed in approximately 17% of experimental eyes after the 7^th session, while the BDNF value was in the normal range.

Conclusion. For the first time, local production of neurotrophic factors in intact eyes was studied. The features of the dynamics of neurotrophic factors depending on the duration of FF were studied. It has been shown that FF has stimulating activity (with an accumulative effect) on local BDNF production. The data obtained seem important for the development of the FF method and its translation into the clinic for visual rehabilitation of patients with neurodegenerative diseases of the retina and indicate the need for further research into the molecular mechanisms that realize the biological effects of FF.